USPTO Patents Application 09898586

What is claimed is:

An isolated polypeptide comprising an amino acid sequence selected from the
group consisting of:

a) a mature form of the amino acid sequence selected from the group consisting
ofSEQ ID NO: X 4, 6, 8, 10, 12, 14, 16, 18, 20, 22,24 or 26;

b) a variant of a mature form of the amino acid sequence selected from the group
consisting ofSEQIDNO: 2, 4, 6, 8, 10, 12, 14, 16, 18,20, 22, 24 or 26,
wherein any amino acid in the mature form is changed to a different amino
acid, provided that no more than 1 5% of the amino acid residues in the
sequence of the mature form are so changed;

c) the amino acid sequence selected from the group consisting of SEQ ID NO: 2,
4, 6, 8, 10, 12, 14, 16, 18,20, 22, 24 or 26;

d) a variant of the amino acid sequence selected from the group consisting of
SEQ ID NO: 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22,24 or 26 wherein any amino
acid specified in the chosen sequence is changed to a different amino acid,
provided that no more than 15% of the amino acid residues in the sequence are
so changed; and

e) a fragment of any of a) through d).

The polypeptide of claim 1 that is a naturally occurring allelic variant of the sequence selected
from the group consisting ofSEQIDNO:2, 4, 6, 8, 10, 12, 14, 16, 18,20, 22, 24 or 26.

The polypeptide of claim 2, wherein the variant is the translation of a single nucleotide
polymorphism.

The polypeptide of claim 1 that is a variant polypeptide described therein, wherein any amino
acid specified in the chosen sequence is changed to provide a conservative substitution.

An isolated nucleic acid molecule comprising a nucleic acid sequence encoding a polypeptide
comprising an amino acid sequence selected from the group consisting of:

a) a mature form of the amino acid sequence given SEQ ID NO: 2, 4, 6, 8, 10, 12,
14, 16, 18,20, 22, 24 or 26;

b) a variant of a mature form of the amino acid sequence selected from the group
consisting ofSEQIDNO: 2,4,6, 8, 10, 12, 14, 16, 18,20, 22,24 or 26

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wherein any amino acid in the mature form of the chosen sequence is changed
to a different amino acid, provided that no more than 1 5% of the amino acid
residues in the sequence of the mature form are so changed;

c) the amino acid sequence selected from the group consisting of SEQ ID NO: 2,
4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24 or 26;

d) a variant of the amino acid sequence selected from the group consisting of
SEQ ID NO: 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24 or 26, in which any amino
acid specified in the chosen sequence is changed to a different amino acid,
provided that no more than 15% of the amino acid residues in the sequence are
so changed;

e) a nucleic acid fragment encoding at least a portion of a polypeptide comprising
the amino acid sequence selected from the group consisting of SEQ ID NO: 2,
4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24 or 26 or any variant of said polypeptide
wherein any amino acid of the chosen sequence is changed to a different
amino acid, provided that no more than 1 0% of the amino acid residues in the
sequence are so changed; and

f) the complement of any of said nucleic acid molecules.

6. The nucleic acid molecule of claim 5, w^herein the nucleic acid molecule comprises the
nucleotide sequence of a naturally occurring allelic nucleic acid variant.

7. The nucleic acid molecule of claim 5 that encodes a variant polypeptide, wherein the variant
polypeptide has the polypeptide sequence of a naturally occurring polypeptide variant.

8. The nucleic acid molecule of claim 5, wherein the nucleic acid molecule comprises a single
nucleotide polymorphism encoding said variant polypeptide.

9. The nucleic acid molecule of claim 5, wherein said nucleic acid molecule comprises a
nucleotide sequence selected from the group consisting of

a) the nucleotide sequence selected from the group consisting of SEQ ID NO: 1,
3,5,7, 9, 11, 13, 15, 17, 19,21,23 or 25;

b) a nucleotide sequence wherein one or more nucleotides in the nucleotide
sequence selected from the group consisting of SEQ ID NO: 1, 3, 5, 7, 9, 11,
13, 15, 17, 19, 21, 23 or 25 is changed from that selected from the group
consisting of the chosen sequence to a different nucleotide provided that no

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more than 1 5% of the nucleotides are so changed;

c) a nucleic acid fragment of the sequence selected from the group consisting of
SEQIDNO: 1,3,5,7,9, 11, 13, 15, 17, 19, 21, 23 or 25; and

d) a nucleic acid fragment wherein one or more nucleotides in the nucleotide
sequence selected from the group consisting of SEQ ID NO: 1, 3, 5, 7, 9, 1 1,
13, 15, 17, 19, 21, 23 or 25 is changed from that selected from the group
consisting of the chosen sequence to a different nucleotide provided that no
more than 15% of the nucleotides are so changed.

10. The nucleic acid molecule of claim 5, wherein said nucleic acid molecule hybridizes under
stringent conditions to the nucleotide sequence selected from the group consisting of SEQ ID
NO: 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23 or 25, or a complement of said nucleotide
sequence.

11. The nucleic acid molecule of claim 5, wherein the nucleic acid molecule comprises a
nucleotide sequence in which any nucleotide specified in the coding sequence of the chosen
nucleotide sequence is changed from that selected from the group consisting of the chosen
sequence to a different nucleotide provided that no more than 1 5% of the nucleotides in the
chosen coding sequence are so changed, an isolated second polynucleotide that is a
complement of the first polynucleotide, or a fragment of any of them.

12. A vector comprising the nucleic acid molecule of claim 11.

13. The vector of claim 12, further comprising a promoter operably linked to said nucleic acid
molecule.

14. A cell comprising the vector of claim 12.

15. An antibody that binds immunospecifically to the polypeptide of claim 1 ,

16. The antibody of claim 1 5, wherein said antibody is a monoclonal antibody.

17. The antibody of claim 15, wherein the antibody is a humanized antibody.

18. A method for determining the presence or amount of the polypeptide of claim 1 in a sample,

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the method comprising:

(a) providing said sample;

(b) introducing said sample to an antibody that binds immunospecifically to the
polypeptide; and

(c) determining the presence or amount of antibody bound to said polypeptide,
thereby determining the presence or amount of polypeptide in said sample.

A method for determining the presence or amount of the nucleic acid molecule of claim 5 in a
sample, the method comprising:

(a) providing said sample;

(b) introducing said sample to a probe that binds to said nucleic acid molecule;

and

(c) determining the presence or amount of said probe bound to said nucleic acid
molecule,

thereby determining the presence or amount of the nucleic acid molecule in said
sample.

A method of identifying an agent that binds to the polypeptide of claim 1, the method
comprising:

(a) introducing said polypeptide to said agent; and

(b) determining whether said agent binds to said polypeptide.

A method for identifying a potential therapeutic agent for use in treatment of a pathology,
vs^herein the pathology is related to aberrant expression or aberrant physiological interactions
of the polypeptide of claim 1, the method comprising:

(a) providing a cell expressing the polypeptide of claim 1 and having a
property or function ascribable to the polypeptide;

(b) contacting the cell with a composition comprising a candidate substance;
and

(c) determining whether the substance alters the property or function ascribable
to the polypeptide;

whereby, if an alteration observed in the presence of the substance is not observed
when the cell is contacted with a composition devoid of the substance, the substance is
identified as a potential therapeutic agent.

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22. A method for modulating the activity of the polypeptide of claim 1 , the method comprising
introducing a cell sample expressing the polypeptide of said claim with a compound that
binds to said polypeptide in an amount sufficient to modulate the activity of the polypeptide.

23. A method of treating or preventing a pathology associated with the polypeptide of claim 1,
said method comprising administering the polypeptide of claim 1 to a subject in which such
treatment or prevention is desired in an amount sufficient to treat or prevent said pathology in
said subject.

24. The method of claim 23, wherein said subject is a human.

25. A method of treating or preventing a pathology associated with the polypeptide of claim 1 ,
said method comprising administering to a subject in which such treatment or prevention is
desired a NOVX nucleic acid in an amount sufficient to treat or prevent said pathology in said
subject,

26. The method of claim 25, wherein said subject is a human.

27. A method of treating or preventing a pathology associated with the polypeptide of claim 1,
said method comprising administering to a subject in which such treatment or prevention is
desired a NOVX antibody in an amount sufficient to treat or prevent said pathology in said
subject.

28. The method of claim 27, wherein the subject is a human.

29. A pharmaceutical composition comprising the polypeptide of claim 1 and a pharmaceutically
acceptable carrier.

30. A pharmaceutical composition comprising the nucleic acid molecule of claim 5 and a
pharmaceutically acceptable carrier.

31. A pharmaceutical composition comprising the antibody of claim 15 and a pharmaceutically
acceptable carrier.

32. A kit comprising in one or more containers, the pharmaceutical composition of claim 29.

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33. A kit comprising in one or more containers, the pharmaceutical composition of claim 30.

34. A kit comprising in one or more containers, the pharmaceutical composition of claim 31.

35. The use of a therapeutic in the manufacture of a medicament for treating a syndrome
associated with a human disease, the disease selected from a pathology associated with the
polypeptide of claim 1, wherein said therapeutic is the polypeptide of claim 1.

36. The use of a therapeutic in the manufacture of a medicament for treating a syndrome
associated with a human disease, the disease selected from a pathology associated with the
polypeptide of claim 1, wherein said therapeutic is a NOVX nucleic acid.

37. The use of a therapeutic in the manufacture of a medicament for treating a syndrome
associated with a human disease, the disease selected from a pathology associated with the
polypeptide of claim 1, wherein said therapeutic is aNOVX antibody.

38. A method for screening for a modulator of activity or of latency or predisposition to a
pathology associated with the polypeptide of claim 1 , said method comprising:

a) administering a test compound to a test animal at increased risk for a
pathology associated with the polypeptide of claim 1, wherein said test animal
recombinantly expresses the polypeptide of claim 1 ;

b) measuring the activity of said polypeptide in said test animal after
administering the compound of step (a); and

c) comparing the activity of said protein in said test animal with the activity of
said polypeptide in a control animal not administered said polypeptide,
wherein a change in the activity of said polypeptide in said test animal relative
to said control animal indicates the test compound is a modulator of latency of,
or predisposition to, a pathology associated with the polypeptide of claim 1 .

39. The method of claim 38, wherein said test animal is a recombinant test animal that expresses
a test protein transgene or expresses said transgene under the control of a promoter at an
increased level relative to a wild-type test animal, and wherein said promoter is not the native
gene promoter of said transgene.

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40. A method for determining the presence of or predisposition to a disease associated with
altered levels of the polypeptide of claim 1 in a first mammalian subject, the method
comprising:

a) measuring the level of expression of the polypeptide in a sample from the first
mammalian subject; and

b) comparing the amount of said polypeptide in the sample of step (a) to the
amount of the polypeptide present in a control sample from a second
mammalian subject known not to have, or not to be predisposed to, said
disease,

wherein an alteration in the expression level of the polypeptide in the first subject as
compared to the control sample indicates the presence of or predisposition to said disease.

41 - A method for determining the presence of or predisposition to a disease associated with
altered levels of the nucleic acid molecule of claim 5 in a first mammalian subject, the
method comprising:

a) measuring the amount of the nucleic acid in a sample from the first
mammalian subject; and

b) comparing the amount of said nucleic acid in the sample of step (a) to the
amount of the nucleic acid present in a control sample from a second
mammalian subject known not to have or not be predisposed to, the disease;

wherein an alteration in the level of the nucleic acid in the first subject as compared to
the control sample indicates the presence of or predisposition to the disease.

42. A method of treating a pathological state in a mammal, the method comprising administering
to the mammal a polypeptide in an amount that is sufficient to alleviate the pathological state,
wherein the polypeptide is a polypeptide having an amino acid sequence at least 95%
identical to a polypeptide comprising the amino acid sequence selected from the group
consisting of SEQ ID NO: 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24 or 26 or a biologically
active fragment thereof

43. A method of treating a pathological state in a mammal, the method comprising administering
to the mammal the antibody of claim 15 in an amount sufficient to alleviate the pathological
state.

44. An isolated polypeptide according to claim 1 comprising an amino acid sequence selected
from the group consisting of:

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a) a mature form of the amino acid sequence selected from the group consisting
ofSEQIDNO: 6;

b) a variant of a mature form of the amino acid sequence selected from the group
consisting of SEQ ID NO: 6, wherein the amino acid in the mature form is
changed to a different amino acid, provided that no more than 1 5% of the
amino acid residues in the sequence of the mature form are so changed;

c) the amino acid sequence selected from the group consisting of SEQ ID NO: 6;

d) a variant of the amino acid sequence selected from the group consisting of
SEQ ID NO: 6 wherein the amino acid specified in the chosen sequence is
changed to a different amino acid, provided that no more than 1 5% of the
amino acid residues in the sequence are so changed; and

e) a fragment of any of a) through d).

45. The polypeptide of claim 44 that is a naturally occurring allelic variant of the sequence
selected from the group consisting of SEQ ID NO: 6.

46. The polypeptide of claim 45, wherein the variant is the translation of a single nucleotide
polymorphism.

47. The polypeptide of claim 44 that is a variant polypeptide described therein, wherein any
amino acid specified in the chosen sequence is changed to provide a conservative
substitution.

48. An isolated nucleic acid molecule according to claim 5 comprising a nucleic acid sequence
encoding a polypeptide comprising an amino acid sequence selected from the group
consisting of:

a) a mature form of the amino acid sequence given SEQ ID NO: 6;

b) a variant of a mature form of the amino acid sequence selected from the group
consisting of SEQ ID NO: 6 wherein the amino acid in the mature form of the
chosen sequence is changed to a different amino acid, provided that no more
than 15% of the amino acid residues in the sequence of the mature form are so
changed;

c) the amino acid sequence selected from the group consisting of SEQ ID NO: 6;

d) a variant of the amino acid sequence selected from the group consisting of
SEQ ID NO: 6, in which the amino acid specified in the chosen sequence is

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changed to a different amino acid, provided that no more than 1 5% of the
amino acid residues in the sequence are so changed;

e) a nucleic acid fragment encoding at least a portion of a polypeptide comprising
the amino acid sequence selected from the group consisting of SEQ ID NO: 6
or any variant of said polypeptide wherein any amino acid of the chosen
sequence is changed to a different amino acid, provided that no more than 10%
of the amino acid residues in the sequence are so changed; and

f) the complement of any of said nucleic acid molecules.

49. The nucleic acid molecule of claim 48, wherein the nucleic acid molecule comprises the
nucleotide sequence of a naturally occurring allelic nucleic acid variant.

50. The nucleic acid molecule of claim 48 that encodes a variant polypeptide, wherein the variant
polypeptide has the polypeptide sequence of a naturally occurring polypeptide variant.

51. The nucleic acid molecule of claim 48, wherein the nucleic acid molecule comprises a single
nucleotide polymorphism encoding said variant polypeptide.

52. The nucleic acid molecule of claim 48, wherein said nucleic acid molecule comprises a
nucleotide sequence selected from the group consisting of

a) the nucleotide sequence selected from the group consisting of SEQ ID NO: 5;

b) a nucleotide sequence wherein one or more nucleotides in the nucleotide
sequence selected from the group consisting of SEQ ID NO: 5 is changed
from that selected from the group consisting of the chosen sequence to a
different nucleotide provided that no more than 1 5% of the nucleotides are so
changed;

c) a nucleic acid fragment of the sequence selected from the group consisting of
SEQ ID NO: 5; and

d) a nucleic acid fragment wherein one or more nucleotides in the nucleotide
sequence selected from the group consisting of SEQ ID NO: 5 is changed
from that selected from the group consisting of the chosen sequence to a
different nucleotide provided that no more than 1 5% of the nucleotides are so
changed.

53. The nucleic acid molecule of claim 48, wherein said nucleic acid molecule hybridizes under

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stringent conditions to the nucleotide sequence selected from the group consisting of SEQ ID
NO: 5, or a complement of said nucleotide sequence.

54. The nucleic acid molecule of claim 48, wherein the nucleic acid molecule comprises a
nucleotide sequence in which any nucleotide specified in the coding sequence of the chosen
nucleotide sequence is changed from that selected from the group consisting of the chosen
sequence to a different nucleotide provided that no more than 1 5% of the nucleotides in the
chosen coding sequence are so changed, an isolated second polynucleotide that is a
complement of the first polynucleotide, or a fragment of any of them.

55. A vector comprising the nucleic acid molecule of claim 54.

56. The vector of claim 55, further comprising a promoter operably linked to said nucleic acid
molecule.

57. A cell comprising the vector of claim 55.

58. An antibody that binds immunospecifically to the polypeptide of claim 44.

59. A method for determining the presence or amount of the polypeptide of claim 44 in a sample,
the method comprising:

(a) providing said sample;

(b) introducing said sample to an antibody that binds immunospecifically to the
polypeptide; and

(c) determining the presence or amount of antibody bound to said polypeptide,
thereby determining the presence or amount of polypeptide in said sample.

60. A method for determining the presence or amount of the nucleic acid molecule of claim 48 in
a sample, the method comprising:

(a) providing said sample;

(b) introducing said sample to a probe that binds to said nucleic acid molecule;

and

(c) determining the presence or amount of said probe bound to said nucleic acid
molecule,

thereby determining the presence or amount of the nucleic acid molecule in said

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sample.

A method of identifying an agent that binds to the polypeptide of claim 44, the method
comprising:

(a) introducing said polypeptide to said agent; and

(b) determining whether said agent binds to said polypeptide.

A method for identifying a potential therapeutic agent for use in treatment of a pathology,
wherein the pathology is related to aberrant expression or aberrant physiological interactions
of the polypeptide of claim 1, the method comprising:

(d) providing a cell expressing the polypeptide of claim 44 and having a
property or function ascribable to the polypeptide;

(e) contacting the cell with a composition comprising a candidate substance:
and

(f) determining whether the substance alters the property or function ascribable
to the polypeptide;

whereby, if an alteration observed in the presence of the substance is not observed
when the cell is contacted with a composition devoid of the substance, the substance is
identified as a potential therapeutic agent.

A method for modulating the activity of the polypeptide of claim 44, the method comprising
introducing a cell sample expressing the polypeptide of said claim with a compound that
binds to said polypeptide in an amount sufficient to modulate the activity of the polypeptide.

A method of treating or preventing a pathology associated with the polypeptide of claim 1,
said method comprising administering the polypeptide of claim 44 to a subject in which such
treatment or prevention is desired in an amount sufficient to treat or prevent said pathology in
said subject.

A method of treating or preventing a pathology associated with the polypeptide of claim 44,
said method comprising administering to a subject in which such treatment or prevention is
desired a NOVX nucleic acid in an amount sufficient to treat or prevent said pathology in said
subject.

A method of treating or preventing a pathology associated with the polypeptide of claim 44,

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said method comprising administering to a subject in which such treatment or prevention is
desired a NOVX antibody in an amount sufficient to treat or prevent said pathology in said
subject.

67. A pharmaceutical composition comprising the polypeptide of claim 44 and a
pharmaceutically acceptable carrier.

68. A pharmaceutical composition comprising the nucleic acid molecule of claim 48 and a
pharmaceutically acceptable carrier.

69. A pharmaceutical composition comprising the antibody of claim 58 and a pharmaceutically
acceptable carrier.

70. A kit comprising in one or more containers, the pharmaceutical composition of claim 67.

71. A kit comprising in one or more containers, the pharmaceutical composition of claim 68.

72. A kit comprising in one or more containers, the pharmaceutical composition of claim 69.

73. The use of a therapeutic in the manufacture of a medicament for treating a syndrome
associated with a human disease, the disease selected from a pathology associated with the
polypeptide of claim 44, wherein said therapeutic is the polypeptide of claim 44.

74. A method for screening for a modulator of activity or of latency or predisposition to a
pathology associated with the polypeptide of claim 44, said method comprising:

a) administering a test compound to a test animal at increased risk for a
pathology associated with the polypeptide of claim 44, wherein said test
animal recombinantly expresses the polypeptide of claim 44;

b) measuring the activity of said polypeptide in said test animal after
administering the compound of step (a); and

c) comparing the activity of said protein in said test animal with the activity of
said polypeptide in a control animal not administered said polypeptide,
wherein a change in the activity of said polypeptide in said test animal relative
to said control animal indicates the test compound is a modulator of latency of,
or predisposition to, a pathology associated with the polypeptide of claim 44.

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75. The method of claim 74, wherein said test animal is a recombinant test animal that expresses
a test protein transgene or expresses said transgene under the control of a promoter at an
increased level relative to a w^i Id-type test animal, and wherein said promoter is not the native
gene promoter of said transgene.

76. A method for determining the presence of or predisposition to a disease associated with
altered levels of the polypeptide of claim 44 in a first mammalian subject, the method
comprising:

a) measuring the level of expression of the polypeptide in a sample from the first
mammalian subject; and

b) comparing the amount of said polypeptide in the sample of step (a) to the
amount of the polypeptide present in a control sample from a second
mammalian subject known not to have, or not to be predisposed to, said
disease,

wherein an alteration in the expression level of the polypeptide in the first subject as
compared to the control sample indicates the presence of or predisposition to said disease.

77. A method for determining the presence of or predisposition to a disease associated with
altered levels of the nucleic acid molecule of claim 48 in a first mammalian subject, the
method comprising:

a) measuring the amount of the nucleic acid in a sample from the first
mammalian subject; and

b) comparing the amount of said nucleic acid in the sample of step (a) to the
amount of the nucleic acid present in a control sample from a second
mammalian subject known not to have or not be predisposed to, the disease;

wherein an alteration in the level of the nucleic acid in the first subject as compared to
the control sample indicates the presence of or predisposition to the disease.

78. A method of treating a pathological state in a mammal, the method comprising administering
to the mammal a polypeptide in an amount that is sufficient to alleviate the pathological state,
wherein the polypeptide is a polypeptide having an amino acid sequence at least 95%
identical to a polypeptide comprising the amino acid sequence selected from the group
consisting of SEQ ID NO: 6 or a biologically active fragment thereof.

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79. A method of treating a pathological state in a mammal, the method comprising administerin
to the mammal the antibody of claim 58 in an amount sufficient to relieve the pathological state

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